Scutera Sara, Argenziano Monica, Sparti Rosaria, Bessone Federica, Bianco Gabriele, Bastiancich Chiara, Castagnoli Carlotta, Stella Maurizio, Musso Tiziana, Cavalli Roberta
Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy.
Department of Drug Science and Technology, University of Turin, 10124 Turin, Italy.
Antibiotics (Basel). 2021 Jan 8;10(1):57. doi: 10.3390/antibiotics10010057.
Multidrug-resistant (MDR) Gram-negative bacteria (GNB), such as and , are responsible for severe hospital-acquired infections. Colistin, despite its toxicity and low tissue penetration, is considered the last resort antibiotic against these microorganisms. Of concern, the use of Colistin has recently been compromised by the emergence of Colistin resistance. Herein, we developed a new formulation consisting of multifunctional chitosan-coated human albumin nanoparticles for the delivery of Colistin (Col/haNPs). Col/haNPs were in vitro characterized for encapsulation efficiency, drug release, stability and cytotoxicity and were evaluated for antibacterial activity against MDR GNB ( and ). Col/haNPs showed sizes lower than 200 nm, high encapsulation efficiency (98.65%) and prolonged in vitro release of Colistin. The safety of the nanoformulation was demonstrated by a negligible cytotoxicity on human fibroblasts and hemolytic activity. Col/haNPs evidenced a high antibacterial effect with a significant decrease in MIC values compared to free Colistin, in particular against Col-resistant strains with a pronounced decline of bacterial growth over time. Moreover, Col/haNPs exhibited an inhibitory effect on biofilm formation that was 4 and 60 fold higher compared to free Colistin, respectively for Colistin susceptible and resistant . Our findings suggest that Col/haNPs could represent a promising Colistin nanocarrier with high antimicrobial activity on MDR GNB.
多重耐药（MDR）革兰氏阴性菌（GNB），如[具体细菌名称1]和[具体细菌名称2]，是严重医院获得性感染的病原体。尽管黏菌素具有毒性且组织穿透力低，但它被认为是对抗这些微生物的最后一道抗生素防线。令人担忧的是，最近黏菌素耐药性的出现使黏菌素的使用受到了影响。在此，我们开发了一种由多功能壳聚糖包被的人白蛋白纳米粒组成的新制剂用于递送黏菌素（Col/haNPs）。对Col/haNPs进行了体外包封率、药物释放、稳定性和细胞毒性表征，并评估了其对MDR GNB（[具体细菌名称1]和[具体细菌名称2]）的抗菌活性。Col/haNPs粒径小于200 nm，具有高包封率（98.65%）且黏菌素在体外释放时间延长。该纳米制剂对人成纤维细胞的细胞毒性和溶血活性可忽略不计，证明了其安全性。与游离黏菌素相比，Col/haNPs表现出高抗菌效果，MIC值显著降低，特别是对耐黏菌素菌株，随着时间推移细菌生长明显下降。此外，Col/haNPs对生物膜形成具有抑制作用，对黏菌素敏感和耐药的[具体细菌名称]，其抑制作用分别比游离黏菌素高4倍和60倍。我们的研究结果表明，Col/haNPs可能是一种对MDR GNB具有高抗菌活性的有前景的黏菌素纳米载体。
